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Pharmaceutics
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Biofilm Busting Strategies for Eradicating Infections
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Biofilm Busting Strategies for Eradicating Infections

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (10 December 2022) | Viewed by 21982

Special Issue Editors

Dr. Jennifer Fiegel

E-Mail Website
Guest Editor
Colleges of Engineering and Pharmacy, The University of Iowa, Iowa City, IA, USA
Interests: drug delivery; lung and skin infections; polymeric nanoparticles and microparticles; dry powder aerosols; lung fluids
Dr. Sanna Maria Sillankorva

E-Mail Website
Guest Editor
Department of Health Cluster/ Nanomedicine, INL - International Iberian Nanotechnology Laboratory, Braga, Portugal
Interests: antibacterial resistance; biofilm control; nosocomial pathogens; bacteriophages; antibiotic alternatives
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is estimated that microbial biofilms impact the management of over 75% of all human infections. The presence of biofilms is associated with the emergence of antimicrobial drug resistance, the development of chronic infections, limitations of the ability of the host immune system to eradicate an infection, and the contamination of medical devices. The critical role of microbial biofilms in the progression and severity of infections has resulted in significant efforts to develop new strategies to combat them.

The focus of this Special Issue of Pharmaceutics will be on recent advances in the development of effective strategies to control, eliminate, and prevent the formation of biofilms. Both research and review articles are welcome.

Dr. Jennifer Fiegel
Dr. Sanna Maria Sillankorva
Guest Editors

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Keywords

  • Bacterial biofilms
  • Biofouling
  • Nano- and microparticles
  • Anti-fouling coatings
  • Bacteriophage
  • Biofilm inhibitors
  • Quorum sensing
  • Antimicrobial resistance
  • Dispersion

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Published Papers (7 papers)

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Research

16 pages, 6668 KiB  
Article
Lactiplantibacillus plantarum KAU007 Extract Modulates Critical Virulence Attributes and Biofilm Formation in Sinusitis Causing Streptococcus pyogenes
by Irfan A. Rather, Mohammad Younus Wani, Majid Rasool Kamli, Jamal S. M. Sabir, Khalid Rehman Hakeem, Ahmad Firoz, Yong-Ha Park and Yan-Yan Hor
Pharmaceutics 2022, 14(12), 2702; https://doi.org/10.3390/pharmaceutics14122702 - 2 Dec 2022
Cited by 4 | Viewed by 1767
Abstract
Streptococcus pyogenes is one of the most common bacteria causing sinusitis in children and adult patients. Probiotics are known to cause antagonistic effects on S. pyogenes growth and biofilm formation. In the present study, we demonstrated the anti-biofilm and anti-virulence properties of Lactiplantibacillus [...] Read more.
Streptococcus pyogenes is one of the most common bacteria causing sinusitis in children and adult patients. Probiotics are known to cause antagonistic effects on S. pyogenes growth and biofilm formation. In the present study, we demonstrated the anti-biofilm and anti-virulence properties of Lactiplantibacillus plantarum KAU007 against S. pyogenes ATCC 8668. The antibacterial potential of L. plantarum KAU007 metabolite extract (LME) purified from the cell-free supernatant of L. plantarum KAU007 was evaluated in terms of minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). LME was further analyzed for its anti-biofilm potential using crystal violet assay and microscopic examination. Furthermore, the effect of LME was tested on the important virulence attributes of S. pyogenes, such as secreted protease production, hemolysis, extracellular polymeric substance production, and cell surface hydrophobicity. Additionally, the impact of LME on the expression of genes associated with biofilm formation and virulence attributes was analyzed using qPCR. The results revealed that LME significantly inhibited the growth and survival of S. pyogenes at a low concentration (MIC, 9.76 µg/mL; MBC, 39.06 µg/mL). Furthermore, LME inhibited biofilm formation and mitigated the production of extracellular polymeric substance at a concentration of 4.88 μg/mL in S. pyogenes. The results obtained from qPCR and biochemical assays advocated that LME suppresses the expression of various critical virulence-associated genes, which correspondingly affect various pathogenicity markers and were responsible for the impairment of virulence and biofilm formation in S. pyogenes. The non-hemolytic nature of LME and its anti-biofilm and anti-virulence properties against S. pyogenes invoke further investigation to study the role of LME as an antibacterial agent to combat streptococcal infections. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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13 pages, 2555 KiB  
Communication
Increased Activities against Biofilms of the Pathogenic Yeast Candida albicans of Optimized Pom-1 Derivatives
by Valerie Amann, Ann-Kathrin Kissmann, Markus Krämer, Imke Krebs, Julio A. Perez-Erviti, Anselmo J. Otero-Gonzalez, Fidel Morales-Vicente, Armando Rodríguez, Ludger Ständker, Tanja Weil and Frank Rosenau
Pharmaceutics 2022, 14(2), 318; https://doi.org/10.3390/pharmaceutics14020318 - 28 Jan 2022
Cited by 8 | Viewed by 3991
Abstract
Antimicrobial peptides (AMPs) are an alternative group for the therapy of infectious diseases, with activity against a wide range of diverse pathogens. However, classical AMPs have significant side effects in human cells due to their unspecific pore formation in biomembranes. Nevertheless, AMPs are [...] Read more.
Antimicrobial peptides (AMPs) are an alternative group for the therapy of infectious diseases, with activity against a wide range of diverse pathogens. However, classical AMPs have significant side effects in human cells due to their unspecific pore formation in biomembranes. Nevertheless, AMPs are promising therapeutics and can be isolated from natural sources, which include sea and freshwater molluscs. The AMPs identified in these organisms show promising antimicrobial activities, as pathogens are mainly fought by innate defence mechanisms. An auspicious candidate among molluscs is the Cuban freshwater snail Pomacea poeyana, from which the peptides Pom-1 and Pom-2 have been isolated and studied. These studies revealed significant antimicrobial activities for both AMPs. Based on the activities determined, Pom-1 was used for further optimization. In order to meet the emerging requirements of improved anti-biofilm activity against naturally occurring Candida species, the six derivatives Pom-1A to F were developed and investigated. Analysis of the derivatives acting on the most abundant naturally occurring Candida yeast Candida albicans (C. albicans) revealed a strong anti-biofilm activity, especially induced by Pom-1 B, C, and D. Furthermore, a moderate decrease in the metabolic activity of planktonic yeast cells was observed. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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18 pages, 4521 KiB  
Article
Rowan Berries: A Potential Source for Green Synthesis of Extremely Monodisperse Gold and Silver Nanoparticles and Their Antimicrobial Property
by Priyanka Singh and Ivan Mijakovic
Pharmaceutics 2022, 14(1), 82; https://doi.org/10.3390/pharmaceutics14010082 - 29 Dec 2021
Cited by 20 | Viewed by 3047
Abstract
Rowanberries (Sorbus aucuparia) are omnipresent in Europe. The medicinal importance of rowanberries is widely known and corresponds to the active ingredients present in the fruits, mainly polyphenols, carotenoids, and organic acids. In the current study, we explored rowanberries for the reduction [...] Read more.
Rowanberries (Sorbus aucuparia) are omnipresent in Europe. The medicinal importance of rowanberries is widely known and corresponds to the active ingredients present in the fruits, mainly polyphenols, carotenoids, and organic acids. In the current study, we explored rowanberries for the reduction of gold and silver salts into nanoparticles. Rowanberries-mediated gold nanoparticles (RB-AuNPs) formed within 5 s at room temperature, and silver nanoparticles (RB-AgNPs) formed in 20 min at 90 °C. The produced nanoparticles were thoroughly characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), dynamic light scattering (DLS), single-particle inductively coupled plasma–mass spectrometry (sp-ICP-MS), thermogravimetric analysis (TGA), Fourier transform-infrared spectroscopy (FT-IR) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). The characterization confirmed that the nanoparticles are highly monodisperse, spherical, stable over long periods, and exhibit a high negative zeta potential values. The produced RB-AuNPs and RB-AgNPs were 90–100 nm and 20–30 nm in size with a thick biological corona layer surrounding them, providing extreme stability but lowering the antimicrobial activity. The antimicrobials study of RB-AgNPs revealed that the nanoparticles have antimicrobial potential with an MBC value of 100 µg/mL against P. aeruginosa and 200 µg/mL against E. coli. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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20 pages, 6068 KiB  
Article
Inhibitory Effects of Cinnamaldehyde Derivatives on Biofilm Formation and Virulence Factors in Vibrio Species
by Olajide Sunday Faleye, Ezhaveni Sathiyamoorthi, Jin-Hyung Lee and Jintae Lee
Pharmaceutics 2021, 13(12), 2176; https://doi.org/10.3390/pharmaceutics13122176 - 17 Dec 2021
Cited by 22 | Viewed by 3920
Abstract
Vibrio parahaemolyticus is considered one of the most relevant pathogenic marine bacteria with a range of virulence factors to establish food-related gastrointestinal infections in humans. Cinnamaldehyde (CNMA) and some of its derivatives have antimicrobial and antivirulence activities against several bacterial pathogens. This study [...] Read more.
Vibrio parahaemolyticus is considered one of the most relevant pathogenic marine bacteria with a range of virulence factors to establish food-related gastrointestinal infections in humans. Cinnamaldehyde (CNMA) and some of its derivatives have antimicrobial and antivirulence activities against several bacterial pathogens. This study examined the inhibitory effects of CNMA and its derivatives on biofilm formation and the virulence factors in Vibrio species, particularly V. parahaemolyticus. CNMA and ten of its derivatives were initially screened against V. parahaemolyticus biofilm formation, and their effects on the production of virulence factors and gene expression were studied. Among the CNMA derivatives tested, 4-nitrocinnamaldehyde, 4-chlorocinnamaldehyde, and 4-bromocinnamaldehyde displayed antibacterial and antivirulence activities, while the backbone CNMA had weak effects. The derivatives could prevent the adhesion of V. parahaemolyticus to surfaces by the dose-dependent inhibition of cell surface hydrophobicity, fimbriae production, and flagella-mediated swimming and swarming phenotypes. They also decreased the protease secretion required for virulence and indole production, which could act as an important signal molecule. The expression of QS and biofilm-related genes (aphA, cpsA, luxS, and opaR), virulence genes (fliA, tdh, and vopS), and membrane integrity genes (fadL, and nusA) were downregulated in V. parahaemolyticus by these three CNMA analogs. Interestingly, they eliminated V. parahaemolyticus and reduced the background flora from the squid surface. In addition, they exhibited similar antimicrobial and antibiofilm activities against Vibrio harveyi. This study identified CNMA derivatives as potential broad-spectrum antimicrobial agents to treat biofilm-mediated Vibrio infections and for surface disinfection in food processing facilities. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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16 pages, 2396 KiB  
Article
Synergy between “Probiotic” Carbon Quantum Dots and Ciprofloxacin in Eradicating Infectious Biofilms and Their Biosafety in Mice
by Yanyan Wu, Guang Yang, Henny C. van der Mei, Linqi Shi, Henk J. Busscher and Yijin Ren
Pharmaceutics 2021, 13(11), 1809; https://doi.org/10.3390/pharmaceutics13111809 - 29 Oct 2021
Cited by 5 | Viewed by 3425
Abstract
Orally administrated probiotic bacteria can aid antibiotic treatment of intestinal infections, but their arrival at their intestinal target site is hampered by killing in the gastrointestinal tract and by antibiotics solely intended for pathogen killing. Carbon-quantum-dots are extremely small nanoparticles and can be [...] Read more.
Orally administrated probiotic bacteria can aid antibiotic treatment of intestinal infections, but their arrival at their intestinal target site is hampered by killing in the gastrointestinal tract and by antibiotics solely intended for pathogen killing. Carbon-quantum-dots are extremely small nanoparticles and can be derived from different sources, including bacteria. Here, we hypothesize that carbon-quantum-dots inherit antibacterial activity from probiotic source bacteria to fulfill a similar role as live probiotics in intestinal infection therapy. Physico-chemical analyses indicated that carbon-quantum-dots, hydrothermally derived from Bifidobacterium breve (B-C-dots), inherited proteins and polysaccharides from their source-bacteria. B-C-dots disrupted biofilm matrices of Escherichia coli and Salmonella typhimurium biofilms through extensive reactive-oxygen-species (ROS)-generation, causing a decrease in volumetric bacterial-density in biofilms. Decreased bacterial densities leave more open space in biofilms and have enhanced ciprofloxacin penetration and killing potential in an E. coli biofilm pre-exposed to probiotic B-C-dots. Pathogenic carbon-quantum-dots hydrothermally derived from E. coli (E-C-dots) did not disrupt pathogenic biofilms nor enhance E. coli killing potential by ciprofloxacin. B-C-dots were biosafe in mice upon daily administration, while E-C-dots demonstrated a decrease in white blood cell and platelet counts and an increase in C-reactive protein levels. Therefore, the way is paved for employing probiotic carbon-quantum-dots instead of viable, probiotic bacteria for synergistic use with existing antibiotics in treating intestinal infections. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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Graphical abstract

14 pages, 2685 KiB  
Article
Sinonasal Stent Coated with Slow-Release Varnish of Chlorhexidine Has Sustained Protection against Bacterial Biofilm Growth in the Sinonasal Cavity: An In Vitro Study
by Alessandra Cataldo Russomando, Ronit Vogt Sionov, Michael Friedman, Irith Gati, Ron Eliashar, Doron Steinberg and Menachem Gross
Pharmaceutics 2021, 13(11), 1783; https://doi.org/10.3390/pharmaceutics13111783 - 25 Oct 2021
Cited by 5 | Viewed by 2392
Abstract
The aim of the study was to develop a sustained-release varnish (SRV) containing chlorhexidine (CHX) for sinonasal stents (SNS) to reduce bacterial growth and biofilm formation in the sinonasal cavity. Segments of SNS were coated with SRV-CHX or SRV-placebo and exposed daily to [...] Read more.
The aim of the study was to develop a sustained-release varnish (SRV) containing chlorhexidine (CHX) for sinonasal stents (SNS) to reduce bacterial growth and biofilm formation in the sinonasal cavity. Segments of SNS were coated with SRV-CHX or SRV-placebo and exposed daily to bacterial cultures of Staphylococcus aureus subsp. aureus ATCC 25923 or Pseudomonas aeruginosa ATCC HER-1018 (PAO1). Anti-bacterial effects were assessed by disc diffusion assay and planktonic-based activity assay. Biofilm formation on the coated stents was visualized by confocal laser scanning microscopy (CLSM) and high-resolution scanning electron microscopy (HR-SEM). The metabolic activity of the biofilms was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. Disc diffusion assay showed that SRV-CHX-coated SNS segments inhibited bacterial growth of S. aureussubsp. aureus ATCC 25923 for 26 days and P. aeruginosa ATCC HER-1018 for 19 days. CHX was released from coated SNS segments in a pH 6 medium up to 30 days, resulting in growth inhibition of S. aureussubsp. aureus ATCC 25923 for 22 days and P. aeruginosa ATCC HER-1018 for 24 days. The MTT assay showed a reduction of biofilm growth on the coated SNS by 69% for S. aureussubsp. aureus ATCC 25923 and 40% for P. aeruginosa ATCC HER-1018 compared to the placebo stent after repeated exposure to planktonic growing bacteria. CLSM and HR-SEM showed a significant reduction of biofilm formation on the SRV-CHX-coated SNS segments. Coating of SNS with SRV-CHX maintains a sustained delivery of CHX, providing an inhibitory effect on the bacterial growth of S. aureussubsp. aureus ATCC 25923 and P. aeruginosa ATCC HER-1018 for approximately 3 weeks. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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17 pages, 2524 KiB  
Article
Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.
by Paulina Czechowicz, Damian Neubauer, Joanna Nowicka, Wojciech Kamysz and Grażyna Gościniak
Pharmaceutics 2021, 13(10), 1589; https://doi.org/10.3390/pharmaceutics13101589 - 30 Sep 2021
Cited by 8 | Viewed by 2132
Abstract
Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm [...] Read more.
Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis. Full article
(This article belongs to the Special Issue Biofilm Busting Strategies for Eradicating Infections)
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